Identification of a Novel Human Peroxiredoxin-6 (PRDX6) Promoter Region Sequence

Abstract

Peroxiredoxin-6 (PRDX6) is an oxidative stress response protein with multiple roles under reactive oxygen species (ROS)-mediated conditions. The multifunctional cytoprotective role of the protein PRDX6 is to maintain cellular homeostasis and membrane integrity through intracellular ROS and phospholipid turnover. The PRDX6 promoter region has been reported in several biological regulations because of its key binding sites. However, the human PRDX6 promoter sequence is not yet fully understood. In this study, we discovered and characterized the proximal promoter sequence of human PRDX6. Interestingly, the identified human PRDX6 promoter was about 1 kb shorter than the one reported in the database. Further studies with the new human PRDX6 promoter analysis will help to understand intracellular ROS and phospholipid turnover to maintain cellular homeostasis. This report provides the human PRDX6 proximal promoter sequence.

Keywords

peroxiredoxin-6 / promoter sequence / deletion / database / BAC clone

References

[1] Knoops B.; Argyropoulou V.; Becker S.; Ferte L.; Kuznetsova O. Multiple Roles of Peroxiredoxins in Inflammation. Mol. Cells 2016, 39, 60-64. https://doi.org/10.14348/molcells.2016.2341.

[2] Lu J.; Holmgren A. The thioredoxin antioxidant system. Free Radic. Biol. Med. 2014, 66, 75-87. https://doi.org/10.1016/j.freeradbiomed.2013.07.036.

[3] Karpenko I.L.; Valuev-Elliston V.T.; Ivanova O.N.; Smirnova O.A.; Ivanov A.V. Peroxiredoxins-The Underrated Actors during Virus-Induced Oxidative Stress. Antioxidants 2021, 10, 977. https://doi.org/10.3390/antiox10060977.

[4] Lee Y.J. Knockout Mouse Models for Peroxiredoxins. Antioxidants 2020, 9, 182. https://doi.org/10.3390/antiox9020182.

[5] Fisher A.B.; Dodia C.; Manevich Y.; Chen J.W.; Feinstein S.I. Phospholipid hydroperoxides are substrates for non-selenium glutathione peroxidase. J. Biol. Chem. 1999, 274, 21326-21334. https://doi.org/10.1074/jbc.274.30.21326.

[6] Kim J.R.; Yoon H.W.; Kwon K.S.; Lee S.R.; Rhee S.G. Identification of proteins containing cysteine residues that are sensitive to oxidation by hydrogen peroxide at neutral pH. Anal. Biochem. 2000, 283, 214-221. https://doi.org/10.1006/abio.2000.4623.

[7] Fisher A.B. Peroxiredoxin 6: A bifunctional enzyme with glutathione peroxidase and phospholipase A(2) activities. Antioxid. Redox Signal. 2011, 15, 831-844. https://doi.org/10.1089/ars.2010.3412.

[8] Fatma N.; Singh D.P.; Shinohara T.; Chylack L.T., Jr. Transcriptional regulation of the antioxidant protein 2 gene, a thiol-specific antioxidant, by lens epithelium-derived growth factor to protect cells from oxidative stress. J. Biol. Chem. 2001, 276, 48899-48907. https://doi.org/10.1074/jbc.M100733200.

[9] Patel P.; Chatterjee S. Peroxiredoxin 6 in Endothelial Signaling. Antioxidants 2019, 8, 63. https://doi.org/10.3390/antiox8030063.

[10] Pacifici F.; Della Morte D.; Capuani B.; Pastore D.; Bellia A.; Sbraccia P.; Di Daniele N.; Lauro R.; Lauro D. Peroxiredoxin6, a Multitask Antioxidant Enzyme Involved in the Pathophysiology of Chronic Noncommunicable Diseases. Antioxid. Redox Signal. 2019, 30, 399-414. https://doi.org/10.1089/ars.2017.7427.

[11] Kim S.; Yu H.; Azam T.; Dinarello C.A. Interleukin-18 Binding Protein (IL-18BP): A Long Journey From Discovery to Clinical Application. Immune Netw. 2024, 24, e1. https://doi.org/10.4110/in.2024.24.e1.

[12] Fatma N.; Kubo E.; Takamura Y.; Ishihara K.; Garcia C.; Beebe D.C.; Singh D.P. Loss of NF-kappaB control and repression of Prdx6 gene transcription by reactive oxygen species-driven SMAD3-mediated transforming growth factor beta signaling. J. Biol. Chem. 2009, 284, 22758-22772. https://doi.org/10.1074/jbc.M109.016071.

[13] Kubo E.; Shibata T.; Singh D.P.; Sasaki H. Roles of TGF beta and FGF Signals in the Lens: Tropomyosin Regulation for Posterior Capsule Opacity. Int. J. Mol. Sci. 2018, 19, 3093. https://doi.org/10.3390/ijms19103093.

[14] Wahlig S.; Lovatt M.; Mehta J.S. Functional role of peroxiredoxin 6 in the eye. Free Radic. Biol. Med. 2018, 126, 210-220. https://doi.org/10.1016/j.freeradbiomed.2018.08.017.

[15] Fatma N.; Kubo E.; Toris C.B.; Stamer W.D.; Camras C.B.; Singh D.P. PRDX6 attenuates oxidative stress- and TGFbeta-induced abnormalities of human trabecular meshwork cells. Free Radic. Res. 2009, 43, 783-795. https://doi.org/10.1080/10715760903062887.

[16] Fatma N.; Kubo E.; Sharma P.; Beier D.R.; Singh D.P. Impaired homeostasis and phenotypic abnormalities in Prdx6-/-mice lens epithelial cells by reactive oxygen species: Increased expression and activation of TGFbeta. Cell Death Differ. 2005, 12, 734-750. https://doi.org/10.1038/sj.cdd.4401597.

[17] Chhunchha B.; Fatma N.; Kubo E.; Rai P.; Singh S.P.; Singh D.P. Curcumin abates hypoxia-induced oxidative stress based-ER stress-mediated cell death in mouse hippocampal cells (HT22) by controlling Prdx6 and NF-kappaB regulation. Am. J. Physiol. Cell Physiol. 2013, 304, C636-C655. https://doi.org/10.1152/ajpcell.00345.2012.

[18] Beaven D.W.; Scott R.S.; Brown L.J. Diabetes care--a continuing challenge. Aust. N. Z. J. Med. 1988, 18, 297-301. https://doi.org/10.1111/j.1445-5994.1988.tb02041.x.

[19] Chowdhury I.; Mo Y.; Gao L.; Kazi A.; Fisher A.B.; Feinstein S.I. Oxidant stress stimulates expression of the human peroxiredoxin 6 gene by a transcriptional mechanism involving an antioxidant response element. Free Radic. Biol. Med. 2009, 46, 146-153.

[20] Chhunchha B.; Kubo E.; Singh P.; Singh D.P. Sumoylation-deficient Prdx6 repairs aberrant Sumoylation-mediated Sp1 dysregulation-dependent Prdx6 repression and cell injury in aging and oxidative stress. Aging 2018, 10, 2284-2315.